The objectives of this project are to determine the relationship between mesenteric blood flow and intestinal secretion and absorption, and to investigate mechanisms whereby the gastrointestinal hormones secretin, cholecystokinin, gastrin, and glucagon produce their mesenteric vascular effects. Anesthetized cats will be used. Secretory responses will be studied using intraluminal intestine perfusion and collection techniques to determine volume, enzyme, and electrolyte output while intestinal blood flow is monitored. Intestinal absorption will be studied using isotope and autoradiographic techniques in perfused jejunal loops. Also, at the villus level, the influence of gastrointestinal hormones on countercurrent exchange and the consequent effect of the countercurrent mechanism on absorption will be assessed. The effect of both vasodilator (5-hydroxytryptamine in low doses, cholecystokinin, secretin) and vasoconstrictor (5-hydroxytryptamine in high doses, norepinephrine) agents will be studied on the microcirculation to determine whether these agents are effective on arteriolar vessels, and radioactive microspheres will be used to evaluate whether perfusion changes at the mucosa-submucosa level provide a functional basis for the processes of secretion and absorption. The possible role of an intestinal nervous vasodilator pathway mediating the vascular response to the hormones and to 5-hydroxytryptamine and a possible interaction between the superior mesenteric periarterial innervation and this pathway will be studied. Intestinal transmural electrical potentials will be recorded and the effect of vasodilator and vasoconstrictor agents on the potential assessed. Also, possible interactions between the gastrointestinal hormones and other endocrine gland hormones (calcitonin, parathormone, vasopressin) will be studied in smooth muscle and animal preparations to evaluate their effects alone and in combination with gastrointestinal hormones on the mesenteric circulation.